Magnetic resonance imaging (MRI) techniques enable noninvasive functional brain mapping with high spatial and temporal resolution. Signal detection in functional MRI (FMRI) is based on the blood oxygenation level dependent effect produced by the different paramagnetic and diamagnetic properties of deoxyhemoglobin and oxyhemoglobin. Neuronal activation, via the neurovascular coupling cascade, is associated with an increase of local oxyhemoglogin and a relative decrease of deoxyhemoglobin in the venous bed which enhances signal intensity in T2*-weighted MR-images.
Due to its advantageous flexibility and the astonishingly detailed spatial and temporal information it provides, FMRI has become the most widely used imaging tool for studying brain function in humans. Nevertheless, until recently, the study of the brain's auditory system has progressed at a considerably slower pace than other functional systems. This is because FMRI studies of the auditory system are confounded by problems arising from the high intensity acoustic noise produced by gradient switching during echo-planar imaging (abbreviated “EPI”). In particular, during operation scanner noise arises when pulses of current are passed through the gradient coil for spatial encoding of the MR signal. Since the gradient coil is placed inside a strong magnetic field, a pulsed Lorenz force is induced. This force vibrates the coil structure, which in turn generates a compression wave in the air that is perceived as the “scanner noise.” Researchers Hedeen and Edelstein, Magn. Reson. Med., Vol. 37, pp. 7–10, 1997, have shown that the response of an MRI gradient system to pulsed currents is linear. Consequently, the sound spectrum generated by a particular gradient current waveform is the product of the frequency response of the gradient system and the Fourier transform of the waveform. The switched gradient field, which is proportional to the gradient current, along read, phase, and slice directions of a conventional EPI gradient pulse sequence is shown in FIG. 1. FIG. 1 also demonstrates the excitation and acquisition timing of the conventional EPI pulse sequence.
Conventional EPI pulse sequence timing used to acquire a single image slice consists of two parts. First, magnetization is excited with a slice selective (radio frequency) RF pulse, sometimes preceded by a fat suppression pulse, followed by navigator echoes, which takes about 5–30 ms. Second, the magnetization is spatially encoded and acquired during an oscillating read gradient (abbreviated “GR”) and a blipped phase encoding gradient (abbreviated “GP”), which takes about 50–130 ms. The read gradient has a trapezoidal or sinusoidal wave form with a period of 0.5 ms to 2.0 ms. The number of positive and negative read gradient lobes is between 50 to 130.
The EPI sequencing thus generates acoustic noise consisting mainly of two components: (1) a first tone with a frequency of 500–2000 Hz and 50–130 ms duration, produced by the read gradient; and (2) an interruption period lasting for 5–30 ms during excitation and navigator echo acquisition, wherein the first tone is interrupted. Consequently, the acoustic noise generated by a conventional EPI pulse sequence is roughly a pulsed tone with frequency of 500–2000 Hz and pulse rate of 7–20 Hz, as visually demonstrated in FIGS. 2a and 2b. It turns out that the human auditory system is particularly sensitive to pulsed tones within this range of pulse, or repetition rates, generated by conventional EPI pulse sequences.
In practice, EPI noise can reach sound pressure levels (SPL) in the range of about 100 decibels (dB), depending on such factors as the specific imaging sequence, type of gradients, brand of scanner, slice thickness, spatial resolution, bandwidth of data acquisition, and size of the subject examined. The background noise that results from generating the EPI pulse sequence actually activates the auditory system and interacts unpredictably with the true experimental stimuli during studies of functional activation tasks, thereby confounding determinations of hearing threshold of experimental stimuli, studies of phonetic discrimination, and studies of foreground-background discrimination. Therefore, contamination of a test subject's response to an experimental auditory stimulus when exposed to environmental noise within the bore of the MRI magnet is of great concern.
As demonstrated by Ogawa et al., Proc. Natl. Acad. Sci., Vol. 89, pp. 5951–5955, 1992, fMRI, which is based on T2* weighted GE-EPI sequences, acquires a differentially high signal in accordance with local blood oxygenation in the brain, an effect known as the “blood oxygenation-level-dependent effect” or “BOLD effect.” The proton signal-intensity alterations, or contrast, created by the BOLD effect occurs as a result of magnetic-susceptibility variation in living tissues. In particular, the magnetic susceptibility variation observed as the BOLD effect is caused by deoxyhemoglobin, which is an endogenous paramagnetic contrast agent. Areas in the brain that are relatively metabolically active (i.e., have more neuronal activation) at the time of FMRI scanning consequently have relatively more oxyhemoglobin, due to the neurovascular coupling cascade, and relatively lower levels of deoxyhemoglobin consumption due to increased blood flow in local venous beds. This relative increase in local oxyhemoglobin with a relative decrease in deoxyhemoglobin results in higher signal intensity in the T2*-weighted MR-images, which is observable as the BOLD effect.
Almost exclusively, GE-EPI sequences are used for fMRI, which provides the following advantages: (a) allows for a very quick image capture (i.e., approximately 70–100 ms per slice); (b) offers a good local resolution (i.e., approximately 2×2×2 mm3); and, (c) with respect to the BOLD effect, provides an optimal echo time TE (i.e., approximately 40–70 ms at 1.5 T, or approximately 20–40 ms at 3T). A typical GE-EPI sequence can be divided into two time segments: (1) the slice selective excitation (i.e., RF-pulse, slice selection gradient with refocuser) time segment and (2) the echo-planer acquisition in the k-space (i.e., oscillating reading gradient and phase coding gradients) time segment. A representative illustration of a conventional working GE-EPI pulse sequence used for fMRI is provided in FIG. 3. However, acoustic noise generated by conventional EPI gradients, as discussed above, is characterized by complex bursts occurring with each imaging slice. With fast fMRI, EPI gradients are repeated eight to twelve times per second and the noise generated excites the auditory cortex. Like other sensory systems, the auditory cortex is highly susceptible to stimulus presentation rates in this range, but responses progressively decrease as repetition rates increase as illustrated by FIG. 4.
As mentioned, during scanning repetition of the GE-EPI measuring sequence creates a characteristic noise gradient in the scanner with a loudness of approximately 90–100 dB volume. Specifically, the gradient coils of the scanner generate noise as their polarities are rapidly changed in accordance with the EPI sequence. This characteristic background noise is largely composed of a high-frequency component (approximately 500–1500 Hz generated by the oscillating reading gradients) and a low frequency component (approximately 10 Hz generated by a repetition of the measurement of approximately 100 ms duration, particularly by means of a 100 ms periodic interruption of the oscillating reading gradient by the layer selection gradient). This loud background noise, which can be best appreciated by listening to the sound recording entitled “conventional-EPI-sound.wav,” incorporated herein by reference, causes various kinds of negative effects in preclinical and clinical FMRI investigations in animals and humans.
Various workgroups, such as by Seifritz et al. (See Science, Vol. 297, pp. 1706–1708 and supporting online materials, 2002), have confirmed that background noise generated by fMRI scanners during scanning creates a negative, confounding effect on imaging. Conventional GE-EPI gradient noise generated by the MRI scanner results in direct neural activation, with BOLD signal enhancement, in the hearing center of scanned human subjects' brains. Other researchers have shown that conventional GE-EPI acoustic noise of the gradient systems may directly induce neuronal and BOLD activation of the auditory cortices, and in other regions of the brain as well, such as in the visual or motor cortices thereby causing interagonism (See Cho et al., Magn. Reson. Med., Vol. 39, pp. 331–335, 1998). Conventional GE-EPI acoustic background noise of the gradient systems negatively influences cognitive exertion, as well as the neural bases for the same, and is generally perceived by patients and test subjects to be disturbing and unsettling. Other researchers have found that GE-EPI gradient noise specifically diminishes the ability to discriminate acoustic speech stimulation (See Shah et al., Neuroimage, Vol. 12, pp. 100–108, 2000), which is particularly disadvantageous in connection with clinical investigations directed to pre-operative localization of the speech center before a neurosurgical intervention (See Sabsevitz et al., Neurology, Vol. 60, pp. 1788–1792, 2003).
In view of these problems arising from background noise, worldwide intensive research is being conducted to reduce the gradient noise of fMRI sequences and several strategies have emerged to overcome this intrinsic problem. Methods for reducing the affects of gradient noise on the auditory system can be divided into three categories: (a) silent MRI sequences, (b) the use of passive and/or active noise reduction devices, and (c) exploiting the delayed onset of the BOLD signal change that follows acoustic stimulation so as to separate gradient noise from experimental stimuli.
The so-called silent sequences, for example BURST (See Hennig and Hodapp., Magma, Vol. 1, pp. 39–48, 1993, and Jakob P M et al, Magn Reson Med. 1998 October;40(4):614–21) and SIMEX (See Loenneker et al., Magma, Vol. 13, pp. 76–81, 2001) sequence technologies, fundamentally allow the gradient noise to be significantly minimized by generating a sound level that is much lower than the sound level of experimentally delivered stimuli. Silent sequences use slowly changing pulse shapes based on soft, or sinusoidal, ramps for all three gradient axes. This technique is generally not applicable to EPI sequences, but it can be applied to alternative acquisition techniques (i.e., FLASH sequences). While the application of silent sequences to fMRI can provide significant noise reduction reaching noise levels as low as 40 dB, this advantage is achieved, however, with a noticeable loss in temporal resolution of the fMRI measurement. In fact, the reduction in temporal resolution occurs at a factor of up to 300, which leads to significant and generally unacceptable lengthening of the measuring period (e.g., it may take several seconds to for each image slice) needed for clinical or scientific investigation. Consequently, this trade off of diminished temporal resolution in exchange for less gradient noise is impractical because the increased amount of scanning time required to make up for the decreased resolution is not commercially viable.
The BURST technique has been used to generate silent and rapid sequences and overcome the temporal resolution problem. The BURST technique utilizes a train of excitation pulses applied during a single, constant magnetic field gradient. This RF-burst generates a train of echoes that can be acquired with a second, single read-out gradient. As a result, the BURST technique does not require rapidly switched magnetic field gradients, which reduces imaging noise to about 40–50 dB. Compared to EPI, silent BURST offers nearly identical imaging speed; however, signal-to-noise ratio (abbreviated “SNR”) is about 5 to 10 times less for BURST sequences than for either new or conventional EPI. In other words, the use of “quiet” fMRI sequences, such as FLASH sequences, results in significantly slower scanning or, in the case of BURST sequences, has an unacceptably bad signal-to-noise ratio compared to EPI sequences.
Other researchers have experimented with methodical approaches for reducing the GE-EPI noise using passive and/or active noise dampening (See Chen et al., IEEE Trans. Biomed. Eng., Vol. 46, pp. 186–191, 1999). The about 10 Hz pulsed background noise generated by the GE-EPI measurement can be passively reduced (e.g., by means of earplugs or headphones) or actively reduced (e.g., by means of a counter noise). The combined use of earmuffs and earplugs can passively attenuate GE-EPI noise by up to 40–50 dB but it cannot be entirely suppressed because noise conduction through body tissue permits up to 50 dB of noise to be conducted to the middle ear.
Active noise dampening techniques utilize an active device that produces a phase-reversed noise emission. If the cancellation noise is emitted inside earmuffs, the technique achieves only about a 20–30 dB reduction in noise because body tissues still conduct noise. While it is difficult to produce noise emissions outside of earmuffs that are exactly phase-reversed to the magnetic gradient noise components, which travel through the body, some success has been achieved by combining active noise reduction techniques with a passive noise reduction technique, thereby achieving noise cancellation as high as 50–60 dB (See Ravicz et al., J. Acoust. Soc. Am., Vol. 108, pp. 1683–1696, 2000). Unfortunately, the characteristic knocking noise (often referred to as “banking”) of EPI gradient noise remains. Passive and/or active noise dampening, therefore, does not lead to completely satisfactory noise reduction because the effectiveness of these techniques depend upon both (a) the amount of noise energy, and (b), in particular, the kind of noise. More specifically, GE-EPI magnetic gradient noise is typically pulsed in character (i.e., banked or banking) and results in direct brain activation. Banking GE-EPI noise stimulates the brain in a manner that uses up cognitive resources and disturbs the test subjects despite attempts to actively and/or passively dampen the noise.
The third technique to diminish the effect of background gradient noise on scanning subjects attempts to separate the EPI scanner noise from experimental noise stimuli by taking advantage of the temporal delay separating neural stimulation from its hemodynamical effects and using an intermittent scanning approach. Generally speaking, the BOLD signal change induced by a neuronal stimulation appears only after a delay that is on the order of a few seconds, and the decay of the BOLD signal to baseline equilibrium takes at least 10 seconds. This delay in the hemodynamic response function can be used to disentangle EPI noise from experimental acoustic stimuli. So, a multislice echo-planar slab of the auditory cortex can be sampled a few times as follows: (a) after an auditory stimulation; (b) before the corresponding BOLD signal decays completely; and (c) before the BOLD response to the gradient noise appears. In order to separate EPI scanner noise effects from the experimental noise stimulus effect, the separation of successive acquisition blocks should be long enough to allow the auditory system to recover from the BOLD response of the preceding noise-producing EPI acquisition period, and the scan period must be short enough so that imaging does not pick up the rising limb of the BOLD response to the gradient noise.
From a practical standpoint, to perform these noise separation techniques, certain assumptions must be made. Assuming a delay time of about 2 seconds between stimulus onset and the BOLD response, and a dispersion time of about 2 seconds, then scanning times shorter than 2 seconds and repetition times (abbreviated “TRs”) of about 15 seconds or longer should be used. This intermittent scanning approach has been termed “clustered” or “sparse” sampling by some researchers (See Edmister et al., Hum. Brain Mapping, Vol. 7, pp. 89–97, 1999; Hall et al., Hum. Brain Mappling, Vol. 7, pp. 213–223, 1999). However, these intermittent scanning methods are unacceptably time consuming due to the TRs of 15 seconds or more when compared to conventional EPI measurement, which uses TRs of about 1 to 3 seconds.
As indicated above, FMRI scanners and scanning methods of the prior art are unable to satisfactorily address the following technical problem. The characteristic, approximately 8–15 Hz pulsed background noise generated during conventional GE-EPI measurement negatively influences the measurable BOLD effect. So, during fMRI measurement of the auditory system of the brain, the background GE-EPI gradient noise is increased and the reserve capacity of the BOLD signal, and therefore the measurable BOLD signal amplitude, is reduced. In addition, during FMRI measurement of the visual and motor systems of the brain, the BOLD signal is changed by means of complex neural, sensorial and cognitive interactions, although the mechanism responsible for these interactions is not completely understood. Consequently, during fMRI experiments investigating higher cognitive functions, the GE-EPI background noise massively detracts from experiments in cognitive ability by distracting and stimulating the test subjects. This same background noise activates various auditory, visual and motor centers in the brain, thereby distorting measurements determining the connection between cognitive ability and neuronal activation in these test subjects.
Other technical problems are also not adequately addressed by the prior art attempts to reduce GE-EPI background noise effects. For example, during pre-operative clarification studies, particularly when the localization of the speech center is desired, the GE-EPI noise adversely influences the ability to detect and define specific functional centers in a patient's brain, as well as the corresponding associated neural and BOLD activation. Furthermore, the GE-EPI noise is disruptive and uncomfortable for patients and test subjects, and this problem is not adequately mitigated by the prior art technologies.
In summary, the prior art technologies for reducing GE-EPI background noise have proven to be inadequate and/or impractical solutions. Quiet sequences cannot be effectively applied to solve the above-named technical problems because noise reduction can only be achieved with a correspondingly disadvantageous reduction in temporal resolution. This loss of temporal information can only be remedied by a several fold lengthening in clinical and experimental fMRI measurements; however, the required increase in scanning time makes the use of quiet sequences impractical. Passive and active noise reduction methods have also failed to provide a satisfactory solution to the above-mentioned noise-related problems because, while noise attenuation is achieved to some degree, a significant residual amount of “banking” still remains to excite the auditory system. However, whatever advantages obtained using passive and/or active noise reduction methods are at least equally obtainable in connection with the use of the “LINA-EPI” method in accordance with the present invention. Lastly, while prior art intermittent scanning techniques may separate the effect of magnetic field gradient noise from the effects of experimental auditory stimuli, this technique requires an unacceptable increase in the amount of scanning time required and does not actually decrease the level of noise experienced by the test subject.
The present invention endeavors to provide an improved LINA-EPI pulse sequencing method for effectively reducing the GE-EPI background noise of an fMRI scan while maintaining the advantages of the prior art technologies directed to solving this problem.
Accordingly, one object of the present invention is to overcome the disadvantages of the prior art methods for reducing gradient noise.
Another object of the present invention is to lessen activation of the brain's auditory system by undesirable magnetic gradient noise, thereby achieving about a 50% reduction in confounding BOLD signal effects.
A further object of the present invention is to lessen interference (See Cho et al., Magn. Reson. Med., Vol. 39, pp. 331–335, 1998) between auditory activation and activation of other sensorial and senso-motor systems.
A still further object of the present invention is to provide less interference (See Mazad et al., J. Cogn. Neurosci, pp. 172–186, 2002) between auditory stimulation and higher cognitive functions by means of lessening magnetic field gradient noise.
A still further object of the present invention is to lessen interference between auditory stimulation, caused by magnetic field gradient noise, and speech recognition, thereby improving preoperative function testing of the speech system (Shah et al., Neuroimage, Vol. 12, pp. 100–108, 2000).
Yet another object of the present invention is to heightened comfort of the patients and test subjects during MRI investigations by reducing GE-EPI gradient noise.
A still further object of the present invention is to overcome the problems of silent FMRI sequences by achieving satisfactory temporal resolution during FMRI experiments while reducing the impact of magnetic field gradient noise by altering the noise spectrum generated during fMRI scanning.
A yet further object of the present invention is to improve the technical possibilities for reducing effects of magnetic field gradient noise in a scanner, either actively and/or passively.
A still further object of the present invention is to reduce the effective impact of GE-EPI magnetic gradient noise during fMRI scanning procedures without significantly lengthening the scanning period required to generate acceptable images.